Methods for manufacturing well structures for low-noise chemical sensors

ABSTRACT

In one implementation, a method for manufacturing a chemical detection device is described. The method includes forming a chemical sensor having a sensing surface. A dielectric material is deposited on the sensing surface. A first etch process is performed to partially etch the dielectric material to define an opening over the sensing surface and leave remaining dielectric material on the sensing surface. An etch protect material is formed on a sidewall of the opening. A second etch process is then performed to selectively etch the remaining dielectric material using the etch protect material as an etch mask, thereby exposing the sensing surface.

BACKGROUND

The present disclosure relates to sensors for chemical analysis, and tomethods for manufacturing such sensors.

A variety of types of chemical sensors have been used in the detectionof various chemical processes. One type is a chemically-sensitive fieldeffect transistor (chemFET). A chemFET includes a source and a drainseparated by a channel region, and a chemically sensitive area coupledto the channel region. The operation of the chemFET is based on themodulation of channel conductance, caused by changes in charge at thesensitive area due to a chemical reaction occurring nearby. Themodulation of the channel conductance changes the threshold voltage ofthe chemFET, which can be measured to detect and/or determinecharacteristics of the chemical reaction. The threshold voltage may forexample be measured by applying appropriate bias voltages to the sourceand drain, and measuring a resulting current flowing through thechemFET. As another example, the threshold voltage may be measured bydriving a known current through the chemFET, and measuring a resultingvoltage at the source or drain.

An ion-sensitive field effect transistor (ISFET) is a type of chemFETthat includes an ion-sensitive layer at the sensitive area. The presenceof ions in an analyte solution alters the surface potential at theinterface between the ion-sensitive layer and the analyte solution,usually due to the dissociation of oxide groups by the ions in theanalyte solution. The change in surface potential at the sensitive areaof the ISFET affects the threshold voltage of the device, which can bemeasured to indicate the presence and/or concentration of ions withinthe solution.

Arrays of ISFETs may be used for monitoring chemical reactions, such asDNA sequencing reactions, based on the detection of ions present,generated, or used during the reactions. See, for example, U.S. Pat. No.7,948,015 to Rothberg et al., which is incorporated by reference herein.More generally, large arrays of chemFETs or other types of chemicalsensors may be employed to detect and measure static and/or dynamicamounts or concentrations of a variety of analytes (e.g. hydrogen ions,other ions, compounds, etc.) in a variety of processes. The processesmay for example be biological or chemical reactions, cell or tissuecultures or monitoring, neural activity, nucleic acid sequencing, etc.

A specific issue that arises in the operation of chemical sensor arraysis the susceptibility of the sensor output signals to noise.Specifically, the noise affects the accuracy of the downstream signalprocessing used to determine the characteristics of the chemical and/orbiological process being detected by the sensors.

It is therefore desirable to provide devices including low noisechemical sensors, and methods for manufacturing such devices.

SUMMARY

In one implementation, a method for manufacturing a chemical detectiondevice is described. The method includes forming a chemical sensorhaving a sensing surface. A dielectric material is deposited on thesensing surface. A first etch process is performed to partially etch thedielectric material to define an opening over the sensing surface andleave remaining dielectric material on the sensing surface. An etchprotect material is formed on a sidewall of the opening. A second etchprocess is then performed to selectively etch the remaining dielectricmaterial using the etch protect material as an etch mask, therebyexposing the sensing surface.

In another implementation, a chemical detection device is described. Thedevice includes a chemical sensor having a sensing surface. A dielectricmaterial has an opening extending to the sensing surface. A sidewallspacer is on a sidewall of the opening. The sidewall spacer has a bottomsurface spaced away from the sensing surface and an inside surfacedefining a reaction region for receiving at least one reactant.

Particular aspects of one more implementations of the subject matterdescribed in this specification are set forth in the drawings and thedescription below. Other features, aspects, and advantages of thesubject matter will become apparent from the description, the drawings,and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates a block diagram of components of a system for nucleicacid sequencing according to an exemplary embodiment.

FIG. 2 illustrates a cross-sectional view of a portion of the integratedcircuit device and flow cell according to an exemplary embodiment.

FIGS. 3A and 3B illustrate cross-sectional and top views respectively ofa representative chemical sensor and corresponding reaction regionaccording to an exemplary embodiment.

FIGS. 4 to 8 illustrate stages in a manufacturing process for forming alow noise chemical sensor and corresponding well structure according toan exemplary embodiment.

DETAILED DESCRIPTION

A chemical detection device is described that includes low noisechemical sensors, such as chemically-sensitive field effect transistors(chemFETs), for detecting chemical reactions within overlying,operationally associated reaction regions.

Applicants have found that a significant amount of the total noise inchemical sensors, such as chemFETs, can be attributed to etchingprocesses involved in forming the overlying reaction regions. Inparticular, subjecting the sensing surface of a chemical sensor toprolonged periods of a high-energy directional etching process can causesignificant noise in the sensor. For example, plasma impinging on thesensing surface can cause charge build up, to the point of causingundesirable changes or damage within the sensor. This accumulated chargecan become trapped in the gate oxide and/or the gate oxide-semiconductorsubstrate interface of the chemFETs, thereby contributing to the noiseand resulting in variations in operation and degradation in performance.

Techniques described herein can reduce or eliminate charge accumulationin the chemical sensors during the formation of the overlying reactionregions. In doing so, low noise chemical sensors with uniformperformance across an array are provided, such that the characteristicsof subsequent chemical reactions can be accurately detected.

FIG. 1 illustrates a block diagram of components of a system for nucleicacid sequencing according to an exemplary embodiment. The componentsinclude a flow cell 101 on an integrated circuit device 100, a referenceelectrode 108, a plurality of reagents 114 for sequencing, a valve block116, a wash solution 110, a valve 112, a fluidics controller 118, lines120/122/126, passages 104/109/111, a waste container 106, an arraycontroller 124, and a user interface 128. The integrated circuit device100 includes a microwell array 107 overlying a sensor array thatincludes chemical sensors as described herein. The flow cell 101includes an inlet 102, an outlet 103, and a flow chamber 105 defining aflow path of reagents over the microwell array 107.

The reference electrode 108 may be of any suitable type or shape,including a concentric cylinder with a fluid passage or a wire insertedinto a lumen of passage 111. The reagents 114 may be driven through thefluid pathways, valves, and flow cell 101 by pumps, gas pressure, orother suitable methods, and may be discarded into the waste container106 after exiting the outlet 103 of the flow cell 101. The fluidicscontroller 118 may control driving forces for the reagents 114 and theoperation of valve 112 and valve block 116 with suitable software.

The microwell array 107 includes an array of reaction regions asdescribed herein, also referred to herein as microwells, which areoperationally associated with corresponding chemical sensors in thesensor array. For example, each reaction region may be coupled to achemical sensor suitable for detecting an analyte or reaction propertyof interest within that reaction region. The microwell array 107 may beintegrated in the integrated circuit device 100, so that the microwellarray 107 and the sensor array are part of a single device or chip.

The flow cell 101 may have a variety of configurations for controllingthe path and flow rate of reagents 114 over the microwell array 107. Thearray controller 124 provides bias voltages and timing and controlsignals to the integrated circuit device 100 for reading the chemicalsensors of the sensor array. The array controller 124 also provides areference bias voltage to the reference electrode 108 to bias thereagents 114 flowing over the microwell array 107.

During an experiment, the array controller 124 collects and processesoutput signals from the chemical sensors of the sensor array throughoutput ports on the integrated circuit device 100 via bus 127. The arraycontroller 124 may be a computer or other computing means. The arraycontroller 124 may include memory for storage of data and softwareapplications, a processor for accessing data and executing applications,and components that facilitate communication with the various componentsof the system in FIG. 1.

The values of the output signals of the chemical sensors indicatephysical and/or chemical parameters of one or more reactions takingplace in the corresponding reaction regions in the microwell array 107.For example, in an exemplary embodiment, the values of the outputsignals may be processed using the techniques disclosed in Rearick etal., U.S. patent application Ser. No. 13/339,846, filed Dec. 29, 2011,based on U.S. Prov. Pat. Appl. Nos. 61/428,743, filed Dec. 30, 2010, and61/429,328, filed Jan. 3, 2011, and in Hubbell, U.S. patent applicationSer. No. 13/339,753, filed Dec. 29, 2011, based on U.S. Prov. Pat. Appl.No. 61/428,097, filed Dec. 29, 2010, which are all incorporated byreference herein in their entirety.

The user interface 128 may display information about the flow cell 101and the output signals received from chemical sensors in sensor array onthe integrated circuit device 100. The user interface 128 may alsodisplay instrument settings and controls, and allow a user to enter orset instrument settings and controls.

In an exemplary embodiment, during the experiment the fluidicscontroller 118 may control delivery of the individual reagents 114 tothe flow cell 101 and integrated circuit device 100 in a predeterminedsequence, for predetermined durations, at predetermined flow rates. Thearray controller 124 can then collect and analyze the output signals ofthe chemical sensors due to chemical reactions occurring in response tothe delivery of the reagents 114.

During the experiment, the system may also monitor and control thetemperature of the integrated circuit device 100, so that reactions takeplace and measurements are made at a known predetermined temperature.

The system may be configured to let a single fluid or reagent contactthe reference electrode 108 throughout an entire multi-step reactionduring operation. The valve 112 may be shut to prevent any wash solution110 from flowing into passage 109 as the reagents 114 are flowing.Although the flow of wash solution may be stopped, there may still beuninterrupted fluid and electrical communication between the referenceelectrode 108, passage 109, and the microwell array 107. The distancebetween the reference electrode 108 and the junction between passages109 and 111 may be selected so that little or no amount of the reagentsflowing in passage 109 and possibly diffusing into passage 111 reach thereference electrode 108. In an exemplary embodiment, the wash solution110 may be selected as being in continuous contact with the referenceelectrode 108, which may be especially useful for multi-step reactionsusing frequent wash steps.

FIG. 2 illustrates cross-sectional and expanded views of a portion ofthe integrated circuit device 100 and flow cell 101. During operation,the flow chamber 105 of the flow cell 101 confines a reagent flow 208 ofdelivered reagents across open ends of the reaction regions in themicrowell array 107. The volume, shape, aspect ratio (such as basewidth-to-well depth ratio), and other dimensional characteristics of thereaction regions may be selected based on the nature of the reactiontaking place, as well as the reagents, byproducts, or labelingtechniques (if any) that are employed.

The chemical sensors of the sensor array 205 are responsive to (andgenerate output signals) chemical reactions within associated reactionregions in the microwell array 107 to detect an analyte or reactionproperty of interest. The chemical sensors of the sensor array 205 mayfor example be chemically sensitive field-effect transistors (chemFETs),such as ion-sensitive field effect transistors (ISFETs). Examples ofchemical sensors that may be used in embodiments are described in U.S.Patent Application Publication No. 2010/0300559, No. 2010/0197507, No.2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082,and U.S. Pat. No. 7,575,865, each which are incorporated by referenceherein.

FIGS. 3A and 3B illustrate cross-sectional and top views respectively ofa representative chemical sensor 350 in the sensor array coupled to acorresponding reaction region 301 in the microwell array according to anexemplary embodiment.

In the illustrated example, the chemical sensor 350 is an ion-sensitivefield effect transistor. The chemical sensor 350 includes a floatinggate structure 318 having a sensor plate 320 separated from the reactionregion 301 by an ion-sensitive layer 316. In the illustrated example,the floating gate structure 318 includes multiple patterned layers ofconductive material within layers of dielectric material 319. Asdescribed in more detail below, the upper surface of the ion-sensitivelayer 316 acts as the sensing surface 317 for the chemical sensor 350.

The ion-sensitive layer 316 may be deposited using various techniques,or naturally grown during one or more of the manufacturing processesused to form the chemical sensor 350. In some embodiments, theion-sensitive layer 316 is a metal oxide, such as an oxide of silicon,tantalum, aluminum, lanthanum, titanium, zirconium, hafnium, tungsten,palladium, iridium, etc.

The ion-sensitive layer 316 may for example be an oxide of the upperlayer of conductive material of the sensor plate 220. For example, theupper layer of the sensor plate 320 may be titanium nitride, and theion-sensitive layer 316 may comprise titanium oxide or titaniumoxynitride. More generally, the ion-sensitive layer 316 may comprise avariety of different materials to facilitate sensitivity to particularions. For example, silicon nitride or silicon oxynitride, as well asmetal oxides such as silicon oxide, aluminum or tantalum oxides,generally provide sensitivity to hydrogen ions, whereas layerscomprising polyvinyl chloride containing valinomycin provide sensitivityto potassium ions. Materials sensitive to other ions such as sodium,silver, iron, bromine, iodine, calcium, and nitrate may also be used.

The chemical sensor 350 also includes a source region 321 and a drainregion 322 within a semiconductor substrate 354. The source region 321and the drain region 322 comprise doped semiconductor material have aconductivity type different from the conductivity type of the substrate354.

Channel region 323 separates the source region 321 and the drain region322. The floating gate structure 318 overlies the channel region 323,and is separated from the substrate 354 by a gate dielectric 352. Thegate dielectric 352 may be for example silicon dioxide. Alternatively,other dielectrics may be used for the gate dielectric 352.

An opening extends through dielectric material 310 to the ion-sensitivelayer 316. The dielectric material 310 may comprise one or more layersof material deposited sequentially. The opening includes a lower portion314 proximate to the ion-sensitive layer 316. An upper portion 315 ofthe opening extends from the lower portion 314 to the upper surface ofthe dielectric material 310.

The upper portion 315 of the opening includes a sidewall spacer 302 on asidewall 303 of the dielectric material 310. As shown in FIG. 3A, thesidewall spacer 302 does not extend down the entire opening to theion-sensitive layer 316. Instead, the sidewall spacer 302 has a bottomsurface spaced away from the ion-sensitive layer 316 by the lowerportion 314 of the opening.

The sidewall spacer 302 includes an inner surface 304 defining an uppersegment of the reaction region 301. A lower segment of the reactionregion 301 is defined by the lower portion 314 of the opening. As aresult of this structure, the sidewall spacer 302 overhangs the lowerportion 314 of the opening, such that the width of the lower segment ofthe reaction region 301 is greater than the width of the upper segmentof the reaction region 301.

The opening through the dielectric material 310 is formed using a twostep etching process, as described in more detail below with respect toFIGS. 4-8. A first etch process partially etches the dielectric material310 to define the upper portion 315 of the opening, and leave remainingdielectric material 310 over the ion-sensitive layer 316. The first etchprocess may be a process which, if continued all the way down to theion-sensitive layer 316, would cause significant charge to accumulate onthe floating gate structure 318. However, by leaving remainingdielectric material 310 on the ion-sensitive layer 316, such chargeaccumulation is precluded. For example, first etch process may forexample be a directional etching process such as RIE, so that theopening can have a high aspect ratio and be accurately and repeatedlydefined, while also not contributing to noise in the chemical sensor350.

The sidewall spacer 302 is then formed on the sidewall 303. Thedielectric material 310 at the lower portion 314 of the openingcomprises material that can be selectively etched relative to thematerial of the sidewall spacer 302. For example, in one embodiment, thedielectric material 310 at the lower portion 314 of the openingcomprises silicon dioxide, and the sidewall spacer 302 comprises siliconnitride. Alternatively, other dielectric and/or electrically conductivematerials may be used. For example, in some embodiments the sidewallspacer 302 may comprise an electrically conductive material such astitanium nitride. An electrically conductive material for the sidewallspacer 302 can reduce the thermal resistance of the reaction region 301when containing solution, which in turn can reduce the overall thermalnoise during operation.

The sidewall spacer 302 then serves as an etch protect layer to retainthe shape of the upper portion 315 during a second etch process used toform the lower portion 314. This second etch process continues theopening and exposes the ion-sensitive layer 316 to define the reactionregion 301.

The second etching process may for example be a wet etch process whichdoes not contribute charge accumulation on the floating gate structure318. Applicants have found that a significant amount of the total noisein ISFETs, can be attributed to the use of high-power directionaletching processes involved in forming the reaction regions. Inparticular, using plasma to etch all the way down to the ion-sensitivelayer 316 can subject the floating gate structure 318 to the plasma forprolonged periods of time. The plasma can cause charge build up on thefloating gate structure 318, to the point of causing undesirable changesor damage to the device. This accumulated charge can become trapped inthe gate dielectric 352 and/or the interface between the gate dielectric352 and the semiconductor substrate 354, thereby contributing to thenoise and resulting in variations in operation and degradation inperformance.

By using a second etching process to which does not accumulate charge onthe floating gate structure 318, noise induced in the chemical sensor350 due to the formation of the reaction region 301 can be eliminated.As a result, the techniques described herein can be used to form lownoise chemical sensors with uniform performance across an array, suchthat the characteristics of chemical reactions can be accuratelymeasured.

As shown in the top view of FIG. 3B, in the illustrated example theopening and the reaction region 301 have circular cross sections.Alternatively, these may be non-circular. For example, the cross-sectionmay be hexagonal.

In operation, the chemical sensor 350 is responsive to (and generates anoutput signal related to) the amount of a charge 324 present onion-sensitive layer 316 opposite the sensor plate 320. Changes in thecharge 324 cause changes in the voltage on the floating gate structure318, which in turn changes in the threshold voltage of the transistor.This change in threshold voltage can be measured by measuring thecurrent in the channel region 323 between the source region 321 and adrain region 322. As a result, the chemical sensor 350 can be useddirectly to provide a current-based output signal on an array lineconnected to the source region 321 or drain region 322, or indirectlywith additional circuitry to provide a voltage-based output signal.Reactants, wash solutions, and other reagents may move in and out of thereaction region 301 by a diffusion mechanism 340.

In an embodiment, reactions carried out in the reaction region 301 canbe analytical reactions to identify or determine characteristics orproperties of an analyte of interest. Such reactions can generatedirectly or indirectly byproducts that affect the amount of chargeadjacent to the sensor plate 320. If such byproducts are produced insmall amounts or rapidly decay or react with other constituents,multiple copies of the same analyte may be analyzed in the reactionregion 301 at the same time in order to increase the output signalgenerated. In an embodiment, multiple copies of an analyte may beattached to a solid phase support 312, either before or after depositioninto the reaction region 301. The solid phase support 312 may bemicroparticles, nanoparticles, beads, solid or porous comprising gels,or the like. For simplicity and ease of explanation, solid phase support312 is also referred herein as a particle. For a nucleic acid analyte,multiple, connected copies may be made by rolling circle amplification(RCA), exponential RCA, or like techniques, to produce an ampliconwithout the need of a solid support.

In various exemplary embodiments, the methods, systems, and computerreadable media described herein may advantageously be used to processand/or analyze data and signals obtained from electronic orcharged-based nucleic acid sequencing. In electronic or charged-basedsequencing (such as, pH-based sequencing), a nucleotide incorporationevent may be determined by detecting ions (e.g., hydrogen ions) that aregenerated as natural by-products of polymerase-catalyzed nucleotideextension reactions. This may be used to sequence a sample or templatenucleic acid, which may be a fragment of a nucleic acid sequence ofinterest, for example, and which may be directly or indirectly attachedas a clonal population to a solid support, such as a particle,microparticle, bead, etc. The sample or template nucleic acid may beoperably associated to a primer and polymerase and may be subjected torepeated cycles or “flows” of deoxynucleoside triphosphate (“dNTP”)addition (which may be referred to herein as “nucleotide flows” fromwhich nucleotide incorporations may result) and washing. The primer maybe annealed to the sample or template so that the primer's 3′ end can beextended by a polymerase whenever dNTPs complementary to the next basein the template are added. Then, based on the known sequence ofnucleotide flows and on measured output signals of the chemical sensorsindicative of ion concentration during each nucleotide flow, theidentity of the type, sequence and number of nucleotide(s) associatedwith a sample nucleic acid present in a reaction region coupled to asensor can be determined.

FIGS. 4 to 8 illustrate stages in a manufacturing process for forming alow noise chemical sensor and corresponding well structure according toan exemplary embodiment.

FIG. 4 illustrates a first stage of forming a dielectric material 310 onthe sensing surface 317 of a chemical sensor 350. In the illustratedexample, the chemical sensor 350 is the ion-sensitive field effecttransistor described above and includes ion-sensitive layer 316 having atop surface acting as the sensing surface 317. The chemical sensor 350may for example be formed using the techniques described in U.S. PatentApplication Publication No. 2010/0300559, No. 2010/0197507, No.2010/0301398, No. 2010/0300895, No. 2010/0137143, and No. 2009/0026082,and U.S. Pat. No. 7,575,865, each which are incorporated by referenceherein.

In the illustrated embodiment, the dielectric material 310 is formed bysequentially depositing a first layer 400 of silicon dioxide, a secondlayer 410 of silicon nitride, a third layer 420 of silicon dioxide, anda fourth layer 430 of silicon nitride. More generally, the dielectricmaterial 310 may comprise one or more layers, and may comprise variousmaterials.

Next, the dielectric material 310 of the structure in FIG. 4 ispartially etched using an etch process to define an opening 500 over thesensing surface 317, resulting in the structure illustrated in FIG. 5.As shown in FIG. 5, the opening 500 includes a sidewall 303, and abottom surface 502 spaced away from the sensing surface 317 by remainingdielectric material 310. This remaining dielectric material 310 preventsthe sensing surface 317 from being subjected to this etch process, sothat charge does not accumulate. As a result, the etch process used toform the opening 500 may be a directional etch process, such as a plasmaetch, so that the opening 500 can be well defined, while at the sametime precluding this etching process from increasing the noise in thechemical sensor 350.

The opening 500 may for example be formed by using a lithographicprocess to pattern a layer of photoresist on the dielectric material 310to define the location of the opening 500, and then anisotropicallyetching the dielectric material 310 using the patterned photoreist as anetch mask. The anisotropic etching of the dielectric material 310 mayfor example be a dry etch process, such as a fluorine based Reactive IonEtching (RIE) process.

In the illustrated example, the etching of the dielectric material 310is carried out using RIE with end point detection, so that the etchingcan stop at or in the first layer 400. The etching may for example beperformed using a single etch chemistry to each all the layers 400, 410,420 and 430. Alternatively, different etch chemistries may be used foreach of the layers.

Next, a conformal layer 600 of etch protect material is formed on thestructure illustrated in FIG. 5, resulting in the structure illustratedin FIG. 6. In the illustrate embodiment, the conformal layer 600comprises silicon nitride and is formed using plasma enhanced chemicalvapor deposition (PECVD). Alternatively, other procedures and materialsmay be used. For example, the conformal layer 600 could be deposited bysputtering, atomic layer deposition (ALD), low pressure chemical vapordeposition (LPCVD), etc. As described in more detail below with respectto FIG. 8, the remaining dielectric material 310 over the sensingsurface 317 (material of layer 400 in this example) comprises materialwhich can be selectively etched relative to the material of theconformal layer 600 when subjected to a chosen etch process.

Next, an anisotropic etching process is performed on the conformal layer600 illustrated in FIG. 6 to form a sidewall spacer 302 of remainingmaterial of layer 600 within the opening, resulting in the structureillustrated in FIG. 7. The anisotropic etching process removes thematerial of the conformal layer 600 on horizontal surfaces at a fasterrate than material on vertical surfaces. The anisotropic etching processmay for example be performed using a RIE or other plasma etchingprocess. Alternatively, other etching processes may be used.

Next, an isotropic etching process is performed on the structureillustrated in FIG. 7 to extend the opening 500 down to the sensingsurface 317 using the sidewall spacer 302 as an etch mask, therebyforming the reaction region 301 and resulting in the structureillustrated in FIG. 8. The isotropic etching process selectively etchesmaterial of the layer 400, relative to the material of the sidewallspacer 302. As a result, the sidewall spacer 302 acts to protect andretain the shape of the upper portion of the opening.

The isotropic etching process may for example be a wet etch process,such as a buffered oxide etch, HF etch chemistry, etc. Alternatively,other etch processes and chemistries may be used.

A wet process results in no charge accumulation on the floating gatestructure 318. As a result, noise induced in the chemical sensor 350 canbe significantly reduced, as compared to the use of directional etchprocesses (e.g. plasma etching) to etch down to the sensing surface 317.In doing so, the techniques described herein can be used to form lownoise chemical sensors with uniform performance across an array, suchthat the characteristics of subsequent chemical reactions can beaccurately measured.

While the present invention is disclosed by reference to the preferredembodiments and examples detailed above, it is to be understood thatthese examples are intended in an illustrative rather than in a limitingsense. It is contemplated that modifications and combinations willreadily occur to those skilled in the art, which modifications andcombinations will be within the spirit of the invention and the scope ofthe following claims.

What is claimed is:
 1. A method for manufacturing a chemical detectiondevice, the method comprising: forming a chemical sensor having asensing surface; depositing a dielectric material on the sensingsurface; performing a first etch process to partially etch thedielectric material to define an opening over the sensing surface andleave remaining dielectric material on the sensing surface; forming anetch protect material on a sidewall of the opening; and performing asecond etch process to selective etching the remaining dielectricmaterial using the etch protect material as an etch mask, therebyexposing the sensing surface.
 2. The method of claim 1, wherein thechemical sensor is a chemically-sensitive field effect transistor, andthe sensing surface is coupled to a channel of the chemically-sensitivefield effect transistor.
 3. The method of claim 2, wherein the sensingsurface is on an upper surface of a floating gate of the field effecttransistor.
 4. The method of claim 1, wherein the first etch process isan anisotropic etch process, and the second etch process is an isotropicetch process.
 5. The method of claim 4, wherein the first etch processis a dry etch process, and the second etch process is a wet etchprocess.
 6. The method of claim 1, wherein the second etch process doesnot accumulate charge on the sensing surface.
 7. The method of claim 1,wherein depositing the dielectric material comprises depositing a firstdielectric material on the sensing surface, and depositing a seconddielectric material on the first dielectric material.
 8. The method ofclaim 1, wherein forming the etch protect material comprises: depositingthe etch protect material on the remaining dielectric material and thesidewall of the opening; and etching the etch protect material to exposethe remaining dielectric material, thereby forming a sidewall spacer ofremaining etch protect material on the sidewall of the opening.
 9. Themethod of claim 8, wherein the sidewall spacer includes a bottom surfacespaced away from the sensing surface.
 10. The method of claim 1, whereinthe chemical sensor generates a sensor signal in response to a chemicalreaction occurring within the reaction region.
 11. The method of claim9, wherein the chemical reaction is a sequencing reaction.
 12. Achemical detection device, comprising: a chemical sensor having asensing surface; a dielectric material having an opening extending tothe sensing surface; and a sidewall spacer on a sidewall of the opening,the sidewall spacer having a bottom surface spaced away from the sensingsurface and having an inside surface defining a reaction region forreceiving at least one reactant.
 13. The chemical detection device ofclaim 12, wherein the dielectric material within a lower portion of theopening comprises material different than that of the sidewall spacer.14. The chemical detection device of claim 12, wherein the chemicalsensor is a chemically-sensitive field effect transistor, and thesensing surface is coupled to a channel of the chemically-sensitivefield effect transistor.
 15. The chemical detection device of claim 14,wherein the sensing surface is on an upper surface of a floating gate ofthe field effect transistor.
 16. The chemical detection device of claim12, wherein the chemical sensor generates a sensor signal in response toa chemical reaction occurring within the reaction region.
 17. Thechemical detection device of claim 16, wherein the chemical reaction isa sequencing reaction.